Searching for an enhanced predictive tool for mutagenicity.

The Multiple Computer Automated Structure Evaluation (MCASE) program was used to evaluate the mutagenic potential of organic compounds. The experimental Ames test mutagenic activities for 2513 chemicals were collected from various literature sources. All chemicals have experimental results in one or more Salmonella tester strains. A general mutagenicity data set and fifteen individual Salmonella test strain data sets were compiled. Analysis of the learning sets by the MCASE program resulted in the derivation of good correlations between chemical structure and mutagenic activity. Significant improvement was obtained as more data was added to the learning databases when compared with the results of our previous reports. Several biophores were identified as being responsible for the mutagenic activity of the majority of active chemicals in each individual mutagenicity module. It was shown that the multiple-database mutagenicity model showed a clear advantage over normally used single-database models. The expertise produced by this analysis can be used to predict the mutagenic potential of new compounds.